Articles of the Month
Every month the Scientific Writer of SSI will choose a couple of articles from the Scandinavian Journal of Immunology that are of special interest. These will be summarized together with a presentation of the first author, when applicable.
Selected articles November 2016
Toll-like receptors in tryptophan metabolism
Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes
F. Orhan, M. Bhat, K. Sandberg, S. Ståhl, F. Piehl , Karolinska Schizophrenia Project (KaSP) consortium, C. Svensson , S. Erhardt and L. Schwieler
In this recent publication, Swedish researchers show that several, but not all, toll-like receptors (TLRs) play a critical role in the communication between immune activation and induction of the kynurenine pathway in healthy human monocytes.
The kynurenine pathway is involved in a broad spectrum of immune responses during different pathological conditions such as, infections, cancer, transplantation and autoimmunity. Interestingly, accumulating evidence also connects neuroactive kynurenine metabolites to both neurodegenerative and psychiatric disorders. In both peripheral and central systems, the kynurenine pathway represents the major route of tryptophan degradation.
TLRs are type I transmembrane glycoproteins that play a key role in the immune response as sensors of infection and tissue damage. The ability of different TLRs to induce the kynurenine pathway in human monocytes is currently unknown. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes.
Funda Orhan, the first author of this publication is a PhD student in Neuropsychoimmunology at Karolinska Institutet in Stockholm. Her main responsibilities during the study were to conceive and perform the experiments, to analyze the data, and to write the manuscript.
– The finding that some TLRs play a critical role in the communications between immune activation and the induction of the kynurenine pathway could help us to differentiate between different disorders having their own signature kynurenine pathway and TLR increases and decreases, she explains.
Deeper understanding of mechanisms responsible for the immune-related induction of the kynurenine pathway will open up new targets through which aberrant tryptophan metabolism can be controlled. Bearing in mind the number of diseases where different kynurenines are suggested to be of importance, discovering such targets will provide novel potential therapeutic strategies.
Numerous studies point to an involvement of disrupted kynurenine pathway and immunological processes in the pathophysiology of schizophrenia.
– To continue our investigations, we will now study the importance of TLRs as a critical link in this regard, Funda Orhan, says. In collaboration with the Karolinska Schizophrenia Project (KASP), a multidisciplinary research consortium that examines the pathophysiology of schizophrenia, we are currently collecting monocytes from first-episode psychosis patients (most of them drug-naïve to antipsychotic treatment) and age- and gender-matched healthy volunteers. Our project in this regard will be focused on changes in the kynurenine pathway in monocytes following stimulation with various TLRs.